Advanced searches left 3/3

Mutation - U.S. Department of Veterans Affairs

Summarized by Plex Scholar
Last Updated: 04 June 2022

* If you want to update the article please login/register

Gonococcal Clinical Strains Bearing a Common gdhR Single Nucleotide Polymorphism That Results in Enhanced Expression of the Virulence Gene lctP Frequently Possess a mtrR Promoter Mutation That Decreases Antibiotic Susceptibility.

"We found a single nucleotide polymorphism in gdhR, which is often present in both new and old gonococcal clinical strains, as well as findings in a proline -to-serine change at amino acid position 6 of GdhR. " In gonococcal strains that contain the mutant protein, this mutation was found to reduce GdhR transcriptional repression at lctP in comparison to wild-type GdhR. We found that gdhR6 impairs the DNA-binding capability of GdhR in lctP without an obvious effect on protein oligomerization by using purified recombinant proteins and in vitro DNA-binding and cross-linking experiments. We discovered a statistical correlation between gdhR6 and the previously described adenine deletion in the promoter of mtrR, encoding the repressor of the mtrCDE module that codes the MtrCDE multidrug efflux pump that can export antibiotics, host microbios, and biocides by using a panel of U. S. and Danish clinical isolates. The frequent association of gdhR6 and the mtrR promoter mutation in these clinical isolates indicates that it has persisted in this genetic background to raise lctP expression, thus increasing virulence. Upstream of lctP, the mutant GdhR protein produced by gdhR6 had a reduced ability to bind to its target DNA sequence. Interestingly, gdhR6 was found in clinical gonococcal strains isolated in the United States and Denmark at a high rate, and it was also associated with a gene mutation that encodes a repressor of both the mtrCDE antimicrobial efflux pump operon and gdhR. ".

Source link: https://doi.org/10.1128/mbio.00276-22


A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction.

"The retinal pigment epithelium's effluid and solute transporters are key elements of the outer blood-retinal barrier. " RPE defects in tvrm77 mice, which have hypopigmented patches in the central retina, are shown in this paper. A disrupted 5' splice donor sequence in tvrm77 mice revealed a defected 5' splice donor sequence in Slc4a5, a sodium bicarbonate cotransporter gene. In tvrm77 RPE relative to controls, the difference was reduced 19. 7-fold, compared to controls, and alternative splice variants were discovered. SLC4A5 was localized to the Golgi apparatus of cultured human RPE cells as well as in apical and basal membranes. As age, detachment worsened, and the outer nuclear layer thickness decreased with age. At all ages, the direct current ERG fast oscillation and light peak were reduced in amplitude, whereas other RPE-associated responses were unaffected. These findings reveal that SLC4A5 functions at the outer blood-retinal barrier, resulting in decreased tissue accumulation and increased light-evoked RPE electrophysiological responses.

Source link: https://doi.org/10.3390/ijms23042220


Loss-of-function mutation in VCP mimics the characteristic pathology as in FTLD-TARDBP.

"The full range of mechanisms behind fronto-temporal dementia with TARDBP/TDP-43 inclusions by VCP disease mutations is uncertain. " VCP is a mediator of FTLD-TARDBP, according to our latest study. In vcp conditional knockout mice, brain atrophy, hormonal shifts, neuronal loss, gliosis, and TARDBP pathology were all present. VCP inactivation was seen on various pages, indicating that VCP mutations are hypomorphic. In addition, proteomic and transcriptomic signatures in vcp cKO mice resemble those of GRN/Protegerulin carriers. According to those systems, VCP is crucial for neuronal longevity by several means, and it may be a therapeutic goal set to restore protein homeostasis in patients with FTLD-TARDBP. ".

Source link: https://doi.org/10.1080/15548627.2021.1985880

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions